Protein-based therapeutics are typically more difficult to administer to patients than other pharmaceuticals. Because the efficacy of a protein is related to its shape, protein-based therapeutics cannot be subjected to conditions that could cause the unfolding, or denaturing, of the protein or proteins contained therein. Consequently, special care is necessary in the preparation, storage, and administration of protein-based therapeutics.
In addition to avoiding any denaturation of the protein, it is often desirable to be able to control the amount of the protein administered to a patient over time. This helps to avoid protein concentrations within the patient that are undesirably high or low or that fluctuate too much from a desired level, and instead helps maintain a steady level of the therapeutic in the patient. To address this, sustained-release (also known as controlled-release/timed-release, etc.) formulations for many therapeutics, including protein-based therapeutics, have been or are currently in development. Sustained-release protein-based therapeutics can be administered by a variety of methods, including but not limited to oral delivery of tablets or capsules, inhalation of powders, implantation, incorporation into a matrix, or topical application of an encapsulated therapeutic from which the protein is gradually released over time.
Surgical sutures are medical devices used to hold body tissues together after an injury or surgery. Most modern sutures are synthetic, including absorbable sutures made of, for example, polyglycolic acid, polylactic acid, polydioxanone or caprolactone, all of which are broken down by various processes including hydrolysis (polyglycolic acid) and proteolytic enzymatic degradation, and the non-absorbable sutures made of, for example, nylon, polyester, or polypropylene. Natural materials used to make sutures include silk and gut. Recently sutures have been coated with antimicrobial substances to reduce the chances of infection. In addition to being made of different materials, sutures come in very specific sizes ranging from #5 (a heavy “braided” suture suitable for orthopedic use) to #11-0 (a fine “monofilament” suture suitable for ophthalmic use). Sutures must be strong enough to hold the tissue securely but flexible enough to be knotted. They must also be hypoallergenic.
There are numerous advantages and disadvantages to both “monofilament” and “braided” sutures. Advantages of the monofilament suture include that it is very smooth and has a low friction in the tissues, the suture runs very easily through the tissues, several continuous stitches can be pulled easily through the tissue without causing damage to the tissue, the surface of the suture tends not to harbor infection-causing microorganisms so stitch abscesses are less common than with a braided suture, and the surface of the suture is less likely to attracts platelets than a braided suture, which reduces the incidence of thrombus formation. Disadvantages include that monofilament sutures are slippery for an assistant to hold, are slippery for knot tying, may kink or snap, require more throws for security than a braided suture, the knots may slip, which is a disadvantage when relying on a stitch not slipping but is actually an advantage when snugging down 2 throws of a knot, the knots may unravel, are intolerant of the twisting effect of a series of stitches, tend to form loops more than a braided suture, are more springy than a braided suture, and have more memory (e.g. resists being straightened if it has been coiled up in its packet) than braided sutures.
The main differences between a monofilament suture and a braided suture is the higher friction and higher compliance exhibited by the braided suture. Advantages of braided sutures include they are less slippery, they are easier to handle, they have less memory (e.g. stretching it will permanently remove most coils and zigzags), they are easier to knot, the knots tend not to slip, fewer throws are needed on knots, and their friction can be used to advantage in subcuticular stitches. Disadvantages include the increased friction means it does not run as easily as a monofilament suture, even with a single stitch, there is a danger of the pull to overcome friction causing damage to the tissues, pulling the braided suture through more than one stitch at a time is hazardous, except for a subcuticular stitch, there is more chance of infection lodging in the braided suture and not being accessible to antibiotics, particularly with a non-absorbable stitch.
In addition to classic sutures, knitted mesh prepared from copolymers of glycolide and lactide is also suitable for use in the methods of the invention. The mesh is particularly suitable to reduce or prevent hernia formation following surgery, in particular, abdominal surgery.
Many different suturing techniques exist. The most common technique is the simple interrupted stitch which is the simplest to perform and is called “interrupted” because the suture thread is cut between each individual stitch. The vertical and horizontal mattress stitches are also interrupted but are more complex and specialized for particular settings. The running or continuous stitch is quicker but risks failing if the suture is cut in just one place; the continuous locking stitch is a more secure version of the running or continuous stitch. The chest drain stitch and corner stitch are variations of the horizontal mattress stitch. Other stitches include the Figure 8 stitch and subcuticular stitch.
Applicants present herewith for the first time the instant invention whose object is to deliver in a controlled manner physiologically relevant growth factors and cytokines at physiologic levels to a wound by adsorbing the compositions onto a suture or a knitted mesh.